Thousands of chemicals in wide commercial use have not been tested for adverse effects on humans, but are present in the environment. Accordingly, there is a need to improve chemical prioritization for in vivo toxicity testing and, ultimately, to find cell-based alternatives for evaluating the large inventory of potentially harmful substances. Quantitative high throughput screening (qHTS) assays are multiple-concentration experiments with an important role in the efforts of the National Toxicology Program to meet these testing challenges and advance toxicology from a predominantly observational science to a predominantly predictive science. qHTS can simultaneously assay thousands of chemicals over a wide chemical space with reduced cost per substance. Previous approaches for making activity calls from qHTS data were based on pharmaceutical applications seeking to minimize false positives and usually relied on heuristics rather than statistical tests to make activity calls. For instance, we developed a three-stage algorithm to classify substances from qHTS data into statistically supported activity categories relevant to toxicological evaluation, seeking to improve sensitivity while minimizing Type I error rate (Shockley, 2012). The first stage of our approach fits a four-parameter Hill equation to find active substances with a robust concentration-response profile within the tested concentration range. The second stage finds relatively potent substances with substantial activity at the lowest tested concentration, substances not captured in the first stage. The third and final stage of the algorithm separates statistically significant profiles from responses that lack statistically compelling support, or inactives. This framework accommodates large volumes of qHTS data, tolerates missing data, and does not require replicate measurements. The three-stage algorithm described above is based on the Hill equation model. However, concentration-response data can be complex and it may be more informative to find alternative patterns in the data not based on fits to sigmoidal curves. We developed a weighted entropy score (WES) as a measure of average activity level in order to rank chemical in qHTS experiments (Shockley, 2014). WES scores can be used to rank all chemicals in a tested library without a pre-specified model structure, or WES can be used to complement existing approaches by ranking returned hits. The performance of WES has been evaluated using data simulated from a Hill model. WES outperforms rankings based on AC50 (estimated concentration of half-maximal response) across the full range of conditions that are typical of qHTS studies. WES and other metrics of compound activity that do not rely on pre-specified model fits can be used to more reliably prioritize chemicals for follow-up studies. Such quantities are more robust activity measures than parameter estimates derived from nonlinear regression model fits to data generated in qHTS experiments which may accompany very large uncertainties (Shockley, 2015).